Parental hesitancy and perception of the COVID-19 vaccine for children below 5 years in Cheras district, Kuala Lumpur.

INTRODUCTION: The use of the COVID-19 vaccine for all children below the age of 5 is expected to be available soon in Malaysia. Hence, this study aimed to assess parental hesitancy and perception of the vaccine. MATERIALS AND METHODS: A cross-sectional study was conducted among parents of children below 5 years of age, from July to September 2022 at two urban primary care clinics in the Cheras district of Kuala Lumpur. Hesitance and perception of the COVID-19 vaccine were assessed using a self-administered questionnaire. RESULTS: A total of 219 completed entries were analysed. The rate of COVID-19 vaccine hesitance for children below the age of 5 was 64.4% (n=141). Univariate analysis showed that vaccine hesitancy was associated with parental age and Muslim religion. The multivariate model showed that younger parents were more likely to be vaccine hesitant compared to older parents. A 1-year increase in parental age showed a 13% decrease in the odds of vaccine hesitancy (AOR 0.87, 95% CI 0.80-0.96). Muslim parents were also more likely to be vaccine hesitant compared to non-Muslim parents (AOR 2.46, 95% CI 1.26-4.79). Most parents perceived correctly that the vaccine can prevent complications and the spread of the disease. However, their main barriers to vaccination were concerns regarding side effects, safety and effectiveness of the vaccine. CONCLUSION: Our study found that parents have a high rate of COVID-19 vaccine hesitancy for children younger than 5 years of age. Vaccine hesitancy was associated with parents' age and religion. Most of them perceived that the vaccine could prevent complications and the spread of COVID-19. Their main barriers towards vaccination were regarding vaccine side effects, safety and effectiveness.

The risk factors for complications and survival outcomes of Klebsiella pneumoniae Bacteraemia in Hospital Canselor Tuanku Muhriz Universiti Kebangsaan Malaysia.

INTRODUCTION: Mortality of Klebsiella pneumoniae (K. pneumoniae) bacteraemia was reported to be on the rise globally. The 30-day mortality rate of K. pneumoniae bacteraemia ranges from 16% to 55% in Beijing, Shanghai, and Taiwan. However, there is a lack of research on the survival outcomes of K. pneumoniae bacteraemia in Malaysia. The objectives of this study were to determine the poor prognostic factors and predictors of 14-day in-hospital mortality from K. pneumoniae bacteraemia. METHODS: This was a retrospective cohort study of patients with K. pneumoniae bacteraemia in Hospital Canselor Tuanku Muhriz Universiti Kebangsaan Malaysia (HCTM). We included adult patients with blood cultures positive for K. pneumoniae between 1 January 2016 and 31 December 2019. Those with polymicrobial bacteraemia were excluded. Medical records were reviewed to obtain the sociodemographic data, gender, underlying comorbidities, invasive procedures at presentation, sources of bacteraemia, and whether appropriate empirical and definitive antibiotics was given on time. Data regarding complications of K. pneumoniae bacteraemia, including liver abscess, endopthalmitis, septic shock, Quick Pitt (qPitt) bacteraemia score defined as hypothermia, hypotension, respiratory failure, cardiac arrest, and altered mental status and stay in intensive care unit (ICU) were also recorded. The main outcome measure used was the survival in 14 days. Summary of statistical analysis was done. RESULTS: A total of 260 patients with K. pneumoniae bacteraemia were included. All patients received appropriate empirical and definitive antibiotics within 24 h of the time that the sample for index blood cultures was obtained. Respiratory infection, septic shock, qPitt bacteraemia score ≥2, solid organ malignancy, stay in ICU, central venous line insertion at presentation, urinary catheterisation at presentation, and in-patient mechanical ventilation were identified as independent predictors of mortality in K. pneumoniae bacteraemia. The rate of complications such as liver abscess, endophthalmitis, ICU admission, and septic shock was not significantly different between survivors and non-survivors. The 14-day in-hospital mortality rate was 12.3%. The median length of hospitalisation was 11 days (IQR 6 - 19) . The predictors of poor prognosis for 14 days in-hospital mortality for K. pneumoniae bacteraemia were as follows: qPitt bacteraemia score ≥2, central venous line insertion, indwelling urinary catheter at presentation, and in-patient mechanical ventilation. Timing from K. pneumoniae bacteraemia event to death among those qPitt bacteraemia scores ≥2 was only for 9 days or less. CONCLUSIONS: The 14-day in-hospital mortality of patients with K. pneumoniae bacteraemia in our setting was low. The qPitt bacteraemia score ≥2 was the strongest predictor of poor prognosis for 14-day in-hospital mortality in patients with K. pneumoniae bacteraemia. The qPitt bacteraemia score should be proposed to be used as a bedside screening tool for gram negative bacteraemia in our daily clinical practice, which is also useful for predicting mortality in critically ill patients.

Disseminated histoplasmosis mimicking an acute appendicitis.

INTRODUCTION: Histoplasmosis can present in a myriad of clinical manifestations, which often makes its diagnosis difficult and occasionally, deceptive. CASE REPORT: We describe a case of a 33 years old gentleman who was clinically diagnosed as acute appendicitis at initial presentation in view of a one-week history of fever, right lower quadrant abdominal pain- and guarding at right iliac fossa. He had thrombocytopenia and lymphopenia on presentation. Mesenteric lymphadenitis and small bowel lesion were found intraoperatively, which was respectively biopsied and resected. Histopathological result confirms disseminated histoplasmosis. Retroviral screen was positive. He was treated with amphotericin B for one week, subsequently switched to oral itraconazole, followed by initiation of highly active antiretroviral therapy (HAART). DISCUSSION: This case illustrates the various nature of histoplasmosis presentation. A high index of suspicion is needed to clinch the diagnosis and subsequently institute prompt treatment as disseminated disease can be fatal if left untreated in an immunosuppressed host.

Intrinsic bioactivity of thyrotropin in human serum is inversely correlated with thyroid hormone concentrations. Application of a new bioassay using the FRTL-5 rat thyroid cell strain.

We have developed a new bioassay for thyrotropin (TSH) in human serum to evaluate bioactivity in normal individuals and patients with different degrees of primary hypothyroidism. Unpurified TSH in serum showed no stimulation of cyclic AMP production in cultured FRTL-5 rat thyroid cells, but after immunopurification showed potent stimulatory activity. Immunoaffinity purification permitted up to 400-fold concentration of serum TSH, allowing bioactivity measurements even in certain normal sera. The limit of detection in the FRTL-5 bioassay was 10 microU of human TSH per 0.5 ml incubate, and half-maximal responses for standard human TSH was 102 +/- 26 (+/- SE) microU/0.5 ml. Immunoaffinity-purified serum TSH varied in bioactivity-to-immunoactivity (B/I) ratios from less than 0.25 to 1.21 among four euthyroid subjects and eight primary hypothyroid patients. An inverse correlation was found between B/I ratios of immunopurified basal TSH and the serum-free T4 (r = -0.7237, P less than 0.01), T4 (r = -0.6650, P less than 0.05), and T3 (r = -0.6382, P less than 0.05). B/I ratios of immunopurified TSH from three hypothyroid patients before and after acute stimulation by thyrotropin-releasing hormone showed no significant change, despite major changes in serum TSH. In summary, the present study shows an inverse relationship between the metabolic status of an individual and the intrinsic bioactivity of TSH.

Outcome of bacteraemia in patients admitted to the adult medical wards of the UKM hospital.

The clinical outcome of bacteraemic patients is influenced by many factors. It is vital to know one's own local hospital epidemiological data so as to provide optimal care to the affected patients. This was a prospective, observational study carried out in the said patient population over a period of four months in the year 2005. One hundred and ninety one patients presented with bacteraemia over the study period. Fifty-two (27%) of the patients died. Mechanical ventilation, inappropriate empirical antibiotic usage, Chinese ethnicity and low serum albumin levels independently affected prognosis. These factors should alert physicians to those patients who require more intensive monitoring and care.

Regulation of thyrotropin (TSH) bioactivity by TSH-releasing hormone and thyroid hormone.

The regulation of TSH biological activity by thyroid hormone and TRH was studied by comparison of pituitary and in vitro secreted TSH from normal and thyroidectomized rats that were alternatively treated with TRH either in vivo or in vitro. Normal and thyroidectomized (3 weeks postthyroidectomy), rats were injected with saline or TRH (100 micrograms) three times over 24 h. Pituitaries were incubated in vitro for 6 h, and six groups of samples from both pituitary and secreted TSH were analyzed: normal (n = 6), thyroidectomized (n = 6), normal and thyroidectomized groups treated with TRH in vitro (n = 2 each) with 10(-8) M TRH added to the incubation medium, and normal and thyroidectomized groups TRH treated in vivo, their incubation medium also supplemented with 10(-8) M TRH (n = 4 each). The biological activity of TSH in pituitary extracts and media was analyzed in terms of the ability to stimulate adenylate cyclase in human thyroid membranes. Thyroidectomy significantly decreased pituitary TSH bioactivity (70%) compared to normal, with no effect on secreted TSH in the medium. TRH, both in vivo and in vitro, when compared to the corresponding untreated groups, produced a significant increase in bioactive TSH in media from both normal (TRH in vivo, 131%; TRH in vitro, 139%) and thyroidectomized samples after TRH in vivo (158%). The TRH effect in the pituitary showed a significant increase in TSH bioactivity from normal samples treated with TRH in vivo (137%), whereas in thyroidectomized pituitary samples with TRH in vitro, TSH bioactivity was decreased (69%). These results indicate that thyroid hormone deficiency and TRH differentially regulate TSH bioactivity. Thyroid hormone deficiency induced a decrease in pituitary TSH bioactivity and favored the effect of TRH on secretion of more bioactive forms. TRH not only induced the formation of more bioactive forms but also stimulated their secretion into the medium.

A sensitive thyrotropin (TSH) bioassay based on iodide uptake in rat FRTL-5 thyroid cells: comparison with the adenosine 3',5'-monophosphate response to human serum TSH and enzymatically deglycosylated bovine and human TSH.

A sensitive in vitro assay based on the uptake of 125I by the FRTL-5 rat thyroid cell line has been applied to the measurement of TSH bioactivity from different sources. In this bioassay various human pituitary reference preparations showed similar potencies; the limit of detection and the half-maximal response were 1.60 +/- 0.1 (+/- SE) and 9.70 +/- 0.40 microU/0.5 ml, respectively; however, when compared to pituitary TSH from other species, human TSH was 29- and 10-fold less biopotent than bovine and rat TSH, respectively. The iodide uptake response to TSH was inhibited by the presence of human serum in a dose-dependent fashion, but pretreatment of serum with 10% polyethylene glycol restored TSH activity. The iodide uptake response was compared to the stimulation of cAMP production in the measurement of serum TSH bioactivity from human samples after immunoaffinity purification. In the cAMP production bioassay, immunoaffinity-purified serum TSH showed increased bioactivity in patients with primary hypothyroidism and TSH-secreting pituitary tumor compared to that in normal subjects, while in the iodide uptake bioassay minimal differences were detected among the different groups. To investigate further structure-function relationships of TSH in FRTL-5 cells we studied the effects of deglycosylated purified pituitary bovine and human TSH on both bioassays. Using two new enzymes, peptide-N-glycosidase and endo-beta-N-acetylglucosaminidase F, we removed one carbohydrate chain from TSH alpha and all three chains from TSH, respectively. In the iodide uptake bioassay both enzymes induced a 2-fold decrease in TSH biopotency, while in the cAMP production bioassay this decrease was only present with peptide-N-glycosidase-treated TSH. In summary, 1) the iodide uptake bioassay system in FRTL-5 cells represents a valid and sensitive method for the measurement of TSH bioactivity from different sources and can be applied to serum samples with elevated TSH concentrations by simple pretreatment with polyethylene glycol without immunoaffinity purification; 2) the enzymatic removal of one carbohydrate chain from both bovine and human TSH significantly decrease their biological activity, assessed as cAMP production and iodide uptake response in FRTL-5 cells, while the removal of three carbohydrate chains induces a significant decrease only in the iodide uptake bioassay: and 3) the disparate results for cAMP and iodide uptake in both human samples and deglycosylated pituitary TSH suggest that in addition to cAMP, other second messengers may play a role in TSH action.

Familial generalized resistance to thyroid hormones: report of three kindreds and correlation of patterns of affected tissues with the binding of [125I] triiodothyronine to fibroblast nuclei.

We here report three kindreds with a total of 19 persons affected with central and peripheral resistance to thyroid hormones: one kindred with 10 affected persons is the largest reported to date. Male to male transmission of the syndrome was evident in two kindreds, consistent with an autosomal dominant mode of inheritance. During several years of follow up, the degree of resistance to thyroid hormones did not ameliorate. Within a given kindred, a given tissue or tissues was consistently more resistant to thyroid hormone than other tissues. The pattern of tissues most affected in one kindred differed from that of another kindred, perhaps reflecting the inherited underlying molecular defects. Members of kindred A frequently had bone involvement, and several had learning disabilities and recurring infections, while most members of kindreds B and C had little bone involvement, but marked hepatic and cardiac resistance to thyroid hormones. Kinetic studies of the binding of [125I] triiodo-L-thyronine to nuclei from skin fibroblasts from affected patients from each of the kindreds demonstrated decreased maximum binding as compared to normal fibroblasts, but there was no correlation between this parameter and other features of the disease. Four of the 19 patients had previously been treated inappropriately with antithyroid therapies, demonstrating how the syndrome may be readily confused with Graves' disease by some clinicians. Behavior or school performance improved in all children treated with thyroid hormones, and a growth spurt was documented in six children, but objective improvement in IQ scores was not demonstrated, suggesting that initiation of hormone therapy at an early age may be important for maximum benefit.

The production and characterization of thyroid-derived T-cell lines in Graves' disease and Hashimoto's thyroiditis.

Although the thyroid gland itself is a major site of the autoimmune response, the study of T-cell function in autoimmune thyroid disease has usually relied on peripheral blood as a source of cells. In this study, we have established thyroid-derived T-cell lines from six patients with Graves' disease and one patient with Hashimoto's thyroiditis by culturing the thyroid lymphocytes on an autologous thyroid follicular cell monolayer in the presence of exogenous interleukin 2 (IL-2). These T-cell lines have allowed in vitro investigation of thyroid-derived T-cell function, an approach which was previously limited by the number of lymphocytes obtained from the gland. The lines were predominantly OKT3, OKT4, and HLA-DR positive but showed heterogeneous proliferative responses. Some lines gave autologous or allogeneic mixed lymphocyte reactions but other did not. Only one of the seven lines responded well to the thyroid antigens thyroglobulin and microsomes presented by autologous monocytes. However, six of the lines proliferated in the presence of live but not dead autologous thyroid follicular cells, particularly when interferon-gamma (IFN-gamma) was added. This treatment has been shown to enhance HLA-DR and -DQ antigen expression by thyroid follicular cells in vitro. Furthermore, the proliferation induced by IFN-gamma-treated thyroid follicular cells was increased when thyroglobulin was also added. Together these results support the hypothesis that the expression of Ia antigens such as HLA-DR by thyroid follicular cells in autoimmune thyroid disease may be important in enhancing the autoimmune response, conferring on these cells the ability to present thyroid autoantigens to T cells. The use of thyroid-derived T-cell lines should permit a more detailed evaluation of the disordered immuno-regulation in Graves' disease and Hashimoto's thyroiditis than has been possible previously.

Thyrotropin-secreting pituitary adenomas: clinical and biochemical heterogeneity. Case reports and follow-up of nine patients.

STUDY OBJECTIVE: To evaluate the clinical and biochemical features of patients with TSH (thyroid-stimulating hormone, thyrotropin)-secreting pituitary tumors; to measure the biologic activity in vitro of circulating TSH from selected patients before and after pituitary surgery. DESIGN: Case series. SETTING: Patients in an endocrinology unit. PATIENTS: Nine patients with TSH-secreting pituitary tumors. MEASUREMENTS AND MAIN RESULTS: All patients had hyperthyroidism, elevated free thyroxine and triiodothyronine levels, and detected levels of TSH. The free alpha subunit, a tumor marker for neoplasms of gonadotropic or thyrotropic cell origin, was elevated in all nine patients. Seven of the nine patients had been treated with thionamides, radioactive iodine, or thyroidectomy for presumed primary hyperthyroidism. The delay from the initial treatment of hyperthyroidism to the correct diagnosis of a pituitary neoplasm was 6.2 +/- 4.8 (mean +/- SD) years. Two of the seven patients with macroadenomas died in the perioperative period (one at NIH, one at a referring hospital). Of the remaining five patients with macroadenomas, four have residual tumor and inappropriate TSH secretion, despite surgery and radiation therapy, at follow-up from 3.5 to 6 years. In contrast, the two patients with microadenomas are clinically cured 2.5 and 4 years after transsphenoidal adenomectomy. The biologic to immunologic (B/I) ratio of serum TSH, determined preoperatively in five patients with TSH-secreting tumors, was elevated compared with euthyroid subjects. In three patients the B/I ratio of serum TSH was also measured after pituitary surgery; in two the elevated B/I ratio returned to normal after successful pituitary adenomectomy, while in the third this ratio remained elevated after incomplete adenoma resection. CONCLUSIONS: With the routine availability of ultrasensitive TSH assays and their increasing use to confirm thyrotoxicosis from all causes, we expect that TSH-secreting pituitary tumors will be diagnosed earlier, before inappropriate antithyroid therapy, permitting an improved outcome.